Using virtual AChE homology screening to identify small molecules with the ability to inhibit marine biofouling

Arabshahi, Homayon John (avtor), Trobec, Tomaž (avtor), Foulon, Valentin (avtor), Hellio, Claire (avtor), Frangež, Robert (avtor), Sepčić, Kristina (avtor), Cahill, Patrick (avtor), Svenson, Johan (avtor)

The search for effective yet environmentally friendly strategies to prevent marine biofouling is hampered by the large taxonomic diversity amongst fouling organisms and a lack of well-defined conserved molecular targets. The acetylcholinesterase enzyme catalyses the breakdown of the neurotransmitter acetylcholine, and several natural antifouling allelochemicals have been reported to display acetylcholinesterase inhibitory activity. Our study is focussed on establishing if acetylcholinesterase can be used as a well-defined molecular target to accelerate discovery and development of novel antifoulants via sequential high-throughput in silico screening, in vitro enzymatic studies of identified compound libraries, and in vivo assessment of the most promising lead compounds. Using this approach, we identified potent cholinesterase inhibitors with inhibitory concentrations down to 3 mM from a 10,000 compound library. The most potent inhibitors were screened against five microfouling marine bacteria and marine microalgae and the macrofouling tunicate Ciona savignyi. No activity was seen against the microfoulers but a potent novel inhibitor of tunicate settlement and metamorphosis was discovered. Although only one of the identified active cholinesterase inhibitors displayed antifouling activity suggesting the link between cholinesterase inhibition and antifouling is limited to certain compound classes, the study highlights how in silico screening employed regularly for drug discovery can also facilitate discovery of antifouling leads.

• Jezik: Angleški jezik
• Ključne besede: homology screening, in silico screening, in vitro enzymatic studies, cholinesterase, AChE inhibitor, antifouling
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: VF - Veterinarska fakulteta ; BF - Biotehniška fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Datum objave: 13.12.2021
• Leto izida: 2021
• Št. strani: 12 str.
• Številčenje: Vol. 8, art. 762287
• PID: 20.500.12556/RUL-133797
• UDK: 636.09:575
• ISSN pri članku: 2296-7745
• DOI: 10.3389/fmars.2021.762287
• COBISS.SI-ID: 89164547
• Datum objave v RUL: 15.12.2021

Gradivo je del revije

• Naslov: Frontiers in marine science
• Skrajšan naslov: Front. mar. sci.
• Založnik: Frontiers Media S.A.
• ISSN: 2296-7745
• COBISS.SI-ID: 523094809

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 15.12.2021